One hallmark of acute lung injury (ALI) is pulmonary edema. Mechanical ventilation of ALI patients with edema tends to over-distend the portions of the lung remaining air filled. The over-distension exacerbates the underlying lung injury and the mortality rate remains above 30%. This proposal aims to test novel methods of reducing ventilator induced lung injury (VILI). Working in the isolated, perfused rat lung preparation, we generate a local edema model by microinfusing albumin solution into subpleural alveoli to elucidate the mechanical effects of heterogeneous liquid-filling or we generate a global, permeability model of edema by including oleic acid in the perfusate. In either model, we image an edematous region by confocal microscopy. We have developed a novel method for determining surface tension in edematous alveoli, enabling in situ assessment of the effect of additives on interfacial surface tension. Using these methods, we will assess the ability of surface tension manipulations and custom-designed ventilation waveforms to protect the edematous lung from VILI.